Sabatini B L, Regehr W G
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Neurosci. 1997 May 15;17(10):3425-35. doi: 10.1523/JNEUROSCI.17-10-03425.1997.
The effect of changes in the shape of the presynaptic action potential on neurotransmission was examined at synapses between granule and Purkinje cells in slices from the rat cerebellum. Low concentrations of tetraethylammonium were used to broaden the presynaptic action potential. The presynaptic waveform was monitored with voltage-sensitive dyes, the time course and amplitude of presynaptic calcium entry were determined with fluorescent calcium indicators, and EPSCs were measured with a whole-cell voltage clamp. Spike broadening increased calcium influx primarily by prolonging calcium entry without greatly affecting peak presynaptic calcium currents, indicating that the majority of calcium channels reach maximal probability of opening in response to a single action potential and that spike broadening increases the open time of these channels. EPSCs were exquisitely sensitive to elevations of calcium influx produced by spike broadening; there was a high power relationship between calcium influx and release such that a 23% increase in spike width led to a 25% increase in total calcium influx, which in turn doubled synaptic strength. The finding that even small changes in spike width influence neurotransmitter release suggests that altering the presynaptic waveform may be an important means of modifying the strength of this synapse. Waveform changes do not, however, contribute significantly to presynaptic modulation via activation of adenosine A1 or GABAB receptors. Furthermore, greatly reducing presynaptic calcium influx did not alter the presynaptic waveform, indicating that calcium channels and calcium-activated channels do not participate in shaping the presynaptic waveform.
在大鼠小脑切片中的颗粒细胞与浦肯野细胞之间的突触处，研究了突触前动作电位形状变化对神经传递的影响。使用低浓度的四乙铵来拓宽突触前动作电位。用电压敏感染料监测突触前波形，用荧光钙指示剂测定突触前钙内流的时间进程和幅度，并用全细胞电压钳测量兴奋性突触后电流（EPSCs）。动作电位展宽主要通过延长钙内流时间来增加钙内流，而对突触前钙电流峰值影响不大，这表明大多数钙通道在单个动作电位作用下达到最大开放概率，且动作电位展宽增加了这些通道的开放时间。EPSCs对动作电位展宽引起的钙内流增加极为敏感；钙内流与递质释放之间存在高度幂函数关系，动作电位宽度增加23%会导致总钙内流增加25%，进而使突触强度加倍。即使动作电位宽度的微小变化也会影响神经递质释放这一发现表明，改变突触前波形可能是调节该突触强度的重要方式。然而，波形变化对通过激活腺苷A1或GABAB受体进行的突触前调制作用不大。此外，大幅降低突触前钙内流并未改变突触前波形，这表明钙通道和钙激活通道不参与塑造突触前波形。
